Oncogenic lncRNA LINC00973 promotes Warburg effect by enhancing LDHA enzyme activity

Through a large-scale functional screening, we identified a long non-coding RNA LINC00973 that is highly expressed in many types of human cancers and can significantly promote tumor cell proliferation in vitro and in vivo. Mechanistically, LINC00973 can bind to the key glycolysis enzyme LDHA (lactate dehydrogenase A) and enhance its enzyme activity, thereby accelerating the aerobic glycolysis of tumor cells, and ultimately promoting tumor cell proliferation. Clinically, high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers. Together, our work demonstrated that LINC00973 modulates a cancer-specific regulation mechanism for the Warburg effect and suggested a potential target against one of cancer’s vulnerabilities for developing broad-acting anti-cancer therapies.